Hematology Board Review
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Transcript Hematology Board Review
Ye Seventeenth of July
Two Thousand and Fourteen
Vince Herrin
A 45 year old woman presents with fatigue and nausea.
She has occasional palpitations and SOB with minimal
exertion. Her cardiac and pulmonary exams are
normal but she has spooning of her nails.
Which of the following should be true?
Low iron, low IBC, low ferritin
B) Low iron, high IBC, high ferritin
C) Low iron, low IBC, high ferritin
D) Low iron, high IBC, low ferritin
A)
Your iron studies are nondiagnostic for a diagnosis of
Iron deficiency. Which of the following would you
order next?
a) Soluble transferrin receptor
b) Beta 2 microglobulin
c) RBC mass
d) ESR
However, remember the gold standard for proving
Iron deficiency anemia is……
?????
Treatment for iron deficiency is best accomplished
with……
a) IV iron replacement weekly
b) IV iron replacement
c) IM iron replacement
d) PO iron replacement
by indices
microcytic/low MCV
iron deficiency
thalassemia
lead poisoning
macrocytic/high MCV
B12/folate deficiency
hemolysis
liver disease
normocytic/normal MCV
-anemia of chronic disease
by RDW
normal
Increased
by reticulocyte response
normal
increased
hemolysis
A 38 yo male patient is referred to you for
recommendations regarding their microcytic anemia.
The patient has no systemic symptoms.
The CBC shows: WBC 5.7 (normal differential), RBC
5.8, Hgb 12, HCT 37.1, platelets 340. MCV is 71 and
RDW is 15.
Ferritin is 50, iron 50, TIBC 300. Hemoglobin
electrophoresis is normal.
Your recommendation should be:
A. Referal for EGD and colonoscopy
B. Iron infusion with a goal of replacing 1000 mg
storage iron
C. Reassurance and a discussion about DNA testing
testing
D. Iron absorption assay followed by 6 months of PO
iron supplementation
Know other anemias…..
Anemia of chronic disease
Hemoglobinopathies
Aplastic anemia
Hemolytic anemias
AIHA
Cold antibodies
microangiopathic
Anemia of inflammation
Unable to utilize available storage iron
Mediated by inflammatory cytokines such as TNF, IL 1,
and IFN beta
Usually associated with a decreased erythropoietin
state or reduced responsiveness to erythropoietin
Clues for diagnosis
Usually normochromic normocytic RBCs
Occasionally may be hypochromic microcytic
Decreased reticulocyte count
Comparison:
Fe deficiency
ACD
Fe
Low
Low
TIBC
High
Low
Transferrin
Saturation
Low
Low/Normal
Ferritin
Low
Normal/High
Differentiate with neurological symptoms
Check vitamin levels
Check antibodies
Suspect diagnosis but vitamin levels normal……
Check MMA and Homocystine
WARM
IgG antibodies
Associated with lymphoproliferative and collagen
vascular diseases
COLD
IgM antibodies
Hemolysis is via the complement pathway
Associated with lymphoproliferative diseases or
infection
CIGAR/PENCIL SHAPES
MACROOVALOCYTES
SPHEROCYTES
SCHISTOCYTES
BITE CELLS
BURR CELLS
SPUR CELLS
TARGET CELLS
TEARDROP CELLS
Primary platelet vs. coagulopathy can be differentiated
by the type of bleeding
Primary platelet bleeding is mucosal with petechia,
epistaxis, gum bleeding and GI tract bleeding
Coagulation cascade bleeds are generally joint and soft
tissue bleeds
A 42 year old female with complaints of epistaxis and
easy bruising for 2 weeks is seen in the ER. She has the
following CBC:
HGB 10
WBC 6200
HCT 30
PLTS 38,000
MCV 72
normal differential
A differential diagnosis includes:
A) Systemic Lupus
B) Hepatitis
C) Drug effect
D) ITP
E) All of the above
Decreased platelets result from
Decreased
Production
Increased
Destruction
Sequestration
As a general rule, if platelets above 20,000 the risk of
spontaneous bleeding is small. When the count goes
below 10,000 then the risk increases substantially and
transfusions should be considered.
Not always idiopathic
30-30-30-10 rule
Idiopathic
Drugs
Disease states such as lymphoma, CLL, collagen
vascular diseases
Viral illnesses such as HCV, HIV
Treatment options:
Platelets > 30,000---observation
Platelets< 30,000---treatment
Steroids
IVIG
Splenectomy
Up to 80% improved with these maneuvers
You are evaluating a 40 yo female patient who fell at
home. She has no known significant medical history.
She is awake but lethargic and has the following test
results of concern:
HCT 27, platelets 45, schistocytes on peripheral smear
BUN 40, creatinine 1.8, LDH 800
Coags are within normal limits; tox screen negative
Your next move after completing your assessment
should be:
A. Send an ADAMTS13 and consult Hematology for
urgent plasmapheresis
B. Order a d-dimer to rule out early DIC
C. One unit random-donor apheresed irradiated
platelets
D. CT Chest/Abdomen/Pelvis to look for occult injury
or PE
DIAGNOSTIC PENTAD
Fever
Neurological signs
Microangiopathic hemolytic anemia
Thrombocytopenia
Renal dysfunction
Newly determined genetic determinant for TTP
ADAMTS13 gene defect found in many patients
Encodes for a vW antigen protease responsible for
cleaving unusually large vW multimers
This syndrome is considered a medical emergency and
treatment should be instituted immediately
Affects about 3% of patients treated with heparin
Less risk with porcine heparin
Less risk with LMWHs
Occurs 5-8 days after starting heparin therapy unless
there has been prior exposure
Amnestic response after prior exposure and can
develop thrombocytopenia within 1-2 days
If platelet count falls by 50% or falls below 100,000
should immediately stop heparin
You are doing a pre-op physical on a healthy 55 yo man
who injured his knee. He has a history of nosebleeds
as a child and his mother was a “free-bleeder” but had
no major episodes and died of an MI at age 74. He tells
you he was once tested for von-Willebrands, but that it
was negative.
His CBC is entirely normal, as are his chemistries.
His coags reveal a PT of 12.5 and a PTT of 40.
You ordered a repeat PTT with a 1:1 mix, which
corrected. Your next step will be:
A. Reassurance and clearance for surgery.
B. Repeat testing for von Willebrand’s disease
C. Order a bleeding time and clear the patient for
surgery if the result is normal.
D. Recommend FFP prior to surgery at a dose of 15
mg/kg to cover whatever coagulation abnormality he
has.
Most common inherited bleeding disorder
Autosomal dominant inheritance
Affected individuals are heterozygous
Bleeding ranges from mild to severe and spontaneous
Prolonged PT/PTT, BT, abnl platelet aggregation with
ristocetin
Von Willebrand factor is a multimeric protein with
two functions
Platelet adhesion---links platelet receptors to exposed
subendothelium
Carrier protein for factorVIII
Type I – quantitative defect
Type 2 – qualitative defects
2b – thrombocytopenia associated
Type 3 – no protein detectable
Also called the giant platelet syndrome
Glycoprotein Ib platelet defect
Unable to bind vWF which is important for adhesion
to the endothelium
Have abnormal ristocetin aggregation
Have mild thrombocytopenia
Autosomal recessive inheritance
Mucosal bleeding
Glycoprotein IIb-IIIa defect
Unable to crosslink fibrinogen which is important for
aggregation
Have abnormal ADP and EPI aggregation
1:1 mix of patient and normal plasma
Will detect a factor deficiency---should see correction with
mix
Will allow detection of an inhibitor---doesn’t correct with
mixing
May need to do a 2 hour incubation to reveal an inhibitor--may correct initially put prolong with incubation if a weak
(slow) inhibitor is present
Hemophilia A and B most common
Third most common
Autosomal recessive inheritance
Correlation between factor level and bleeding
tendency is poor
Less spontaneous bleeding
Treat with FFP
Deficiency is very rare
Acquired deficiency occurs with amyloidosis****
Treat with FFP
XII is also known as the Hageman factor
Have very prolonged PTT
No evidence of clinical bleeding and have normal
hemostasis
A healthy 50 yo female has followed with your for
several years and comes in with right leg swelling that
has been present for about 3 weeks. She is on no
medications except amlodipine. She has not injured
herself, been ill lately, or been on any trips. Her BMI is
24.
You are suspicious based on the exam and order a
Doppler which reveals subacute nearly occlusive clot in
the right superficial femoral vein.
Her CBC, chemistries, and coags are all wnl. Your
recommendation to her is:
A. Take aspirin, use warm soaks and wear support hose
because this is superficial thrombophlebitis.
B. Admit to the hospital for tPA infusion to prevent varicose
vein formation.
C. Order a JAK-2 analysis to assess occult myeloproliferative
disease
D. Recommend at least 6 months of anticoagulation, initiating
LMW heparin and warfarin today.
E. 3 months of anticoagulation beginning with Lovenox for a
week and then warfarin loading at 10mg per day for 3 days
Hypercoaguable states result in unprovoked
thrombosis
Generally there is a family history of thrombosis
Most are undefined but there are several deficiencies
of the natural occurring anticoagulants that are
described
Protein may be decreased or dysfunctional
Check level prior to initiation of Heparin
PROTEIN C DEFICIENCY
Should measure prior to the initiation of Warfarin
therapy
PROTEIN S DEFICIENCY
Functions as a cofactor with Protein C
Should measure prior to the initiation of Warfarin
therapy
Mutation in factor V resulting in resistance to
Activated Protein C
Most common cause is Factor V Leiden mutation
Most common inherited hypercoaguable defect
Found in up to 25% of patients with recurrent
thrombosis
Additive to other risk factors (OCPs, pregnancy, other
defects)
Prolonged PTT
Paradoxical clotting
may be venous or arterial
Recurrent spontaneous fetal loss
A 72 year old man presents with fatigue and bruising.
He has been noted to be mildly pancytopenic with a
CBC as follows:
Hgb 9.4
WBC 2300
segs 35
HCT 28
Plt ct 65,000
monos 45
MCV 102
Retic 0.4%
lymphs 20
His peripheral smear shows basophilic stippling and a
dimorphic population.
The best diagnosis for this case would be:
A) Lymphoma with a leukemic phase
B) Sickle Cell disease
C) Evans syndrome
D) Myelodysplasia
E) Chronic lymphocytic leukemia
Peripheral smear and lab findings suggestive of a MDS
state include
Dimorphic RBC population
Macrocytic RBC’s
Pseudo Pelger-Huet anomaly
Large agranular platelets
Decreased reticulocyte count
Cytogenetics
Primarily see abnormalities of chromosomes 5,7,or 8
Trisomy 8 very common
5q- syndrome has a more favorable prognosis and
is usually found in females with thrombocytosis
Abnormalities of chr 11 with secondary MDS
A 45 year old woman presents with fatigue, early satiety
and bruising. She has noted some night sweats and a
10 pound weight loss over the last 6 weeks. Her PE is
remarkable for splenomegaly and large ecchymosis.
Her CBC is as follows:
HGB 10
WBC 250,500
HCT 31
Plts 675,000
MCV 78
What would you like to see next?
A) Platelet aggregations
B) Coagulation studies
C) Iron studies
D) WBC differential
What is the most likely diagnosis?
A) Chronic Myeloid Leukemia
B) Polycythemia vera
C) Acute Myeloid Leukemia
D) Chronic Lymphocytic Leukemia
Polycythemia vera
Essential Thrombocytosis
Myelofibrosis
Chronic Myeloid Leukemia
Peripheral blood looks like marrow
Basophilia/Eosinophilia
Decreased LAP
Philadelphia chromosome -- t(9,22)
Moves the abl proto-oncogene on chr 9 to the bcr
region on chr 22
Results in production of an abnormal tyrosine kinase
Natural disease progression
CHRONIC PHASE
ACCELERATED PHASE
BLAST CRISIS
Imatinib , et al
Prototype in the class of drugs designed to take
advantage of the t(9,22) abnormality
A tyrosine kinase inhibitor
Many patients with cytogenetic remissions but
duration unknown
Few side effects—N/V/D, cytopenias
Diagnosis requires exclusion of secondary causes of
erythrocytosis
Gaisbock’s syndrome
Hypoxic states
Renal disease
Malignancy
VERA
LOW ERYTHROPOIETIN levels
JAK-2 association
TREAT with PHLEBOTOMY
LEUKEMIA/MYELOFIBROSIS
SECONDARY
HYPOXIA
PHLEBOTOMY
NO LEUKEMIA risk
By definition - thrombocytosis sustained over 6
months that is unexplained
May be associated with splenomegaly but not usually
massive
No clear diagnostic tests exist
Must rule out other causes for “reactive”
thrombocytosis
Iron deficiency anemia
Malignancy
Collagen vascular disease
Infection
Postsplenectomy state
Other MPDs
Characterized by a myelophthisic picture on
peripheral smear
Teardrop-shaped RBC’s
NRBC’s
Left shifted WBC series
Anemic
LAP nondiagnostic
Clues on peripheral smear
Blasts==Acute leukemia
Auer rods == myeloid blasts
Mature cells==Chronic leukemia
Mature lymphocytes==CLL
Mature segs==CML
Work up includes
A bone marrow aspirate and biopsy
Special stains on marrow or peripheral blood
Flow cytometry on marrow or peripheral blood
Cytogenetic studies on marrow
M0
UNDIFFERENTIATED
M1
WITHOUT MATURATION
M2
WITH MATURATION
M3
PROMYELOCYTIC
M4
MYELOMONOCYTIC
M5
MONOCYTIC
M6
ERYTHROID
M7
MEGAKARYOCYTIC
M2
With t(8,21) has a good prognosis
M4
With inverted 16 and associated eosinophilia is a good
prognostic category
M3
Associated with t(15,17)
Translocation involving the retinoic acid receptor gene
Good prognosis category
Prominent Auer rods
Commonly associated with DIC
M5
Commonly associated with skin and soft tissue
disease
Gingival hyperplasia
CNS disease may occur
Treatment scheme:
Induction chemotherapy—designed to take a patient
to aplasia with recovery of “normal” hematopoiesis and
a remission state
Consolidation chemotherapy– designed to reinforce
the remission obtained. Usually multiple cycles given
Treatment for APL is different
Based on the translocation of the retinoic acid receptor
Uses All Trans Retinoic Acid (ATRA) as a maturational
agent
Must also include chemotherapy with at least an
anthracycline
Heparin usually not necessary
Primarily occurs in children
Lymphadenopathy and splenomegaly occur in 50%
An anterior mediastinal mass is common with the T-
cell subtypes
CNS disease is common
L1
CHILDHOOD
L2
ADULT
L3
BURKITT’S
Treatment scheme
Induction chemotherapy with multi-drug regimens
Consolidation chemotherapy with multi- drug
regimens for multiple cycles
important drugs include Vincristine, prednisone and
anthracyclines
Treatment scheme cont
Maintenance chemotherapy is an important part of
ALL treatment and lasts for several cycles
CNS prophylaxis is also necessary with chemotherapy
+/- radiation therapy
An 80 year old woman is seen for her yearly check up.
She feels well. A screening CBC is done and has the
following values.
Hgb 7
WBC 55,000 lymphs 98%
HCT 20
Plts 40,000
Her physical exam is remarkable for 2 cm
lymphadenopathy in the cervical chain. Her peripheral
smear looks like this:
What is this disease?
A) CML
B) CLL
C) HCL
D) PLL
Which of the following statements is true?
A) She has stage IV disease
B) She should be observed rather than treated at this
stage
C) Her life expectancy from this leukemia is less than 6
months
D) This is a leukemoid reaction
The most common leukemia in the western countries
Typically a disease of older individuals
Flow cytometry is usually diagnostic
Typically a B cell disorder
CD19,CD20,CD23 Positive
CD5 Positive
RAI staging system
Survival
O Lymphocytosis
I Lymphadenopathy
II Splenomegaly
III Anemia
IV Thrombocytopenia
> 10 yrs
6-7 yrs
6-7 yrs
2-3 yrs
2-3 yrs
Treatment options include
Observation –many patients have no indication for
therapy at the time of presentation
Indications for treatment include
Symptomatic disease
Rapid doubling of the WBC count
Anemia
Thrombocytopenia
Complications include
Hypogammaglobulinemia
Treatment with IVIG may be of benefit
Autoimmune disorders such as AIHA or ITP
Treat with high dose steroids
Treat disease as well
Commonly associated with second malignancies
Lung cancer
Head and neck cancer
B cell phenotype-- CD 19,CD20 Positive
also CD 11C, CD 25, and CD 103 Positive
Increased risk for infections
Affects males 4:1 over females
Usual presentation is
Pancytopenia
Large splenomegaly
Inaspirable bone marrow
A 24 year old girl presents with painless
lymphadenopathy in her cervical chain that measures
up to 3 cm. She is asymptomatic and has not had any
recent URI symptoms.
Physical exam is pertinent for the lymph nodes
mentioned as well as several small inguinal nodes
measuring 2-3 cm.
She has an FNA of an inguinal node that is
nondiagnostic.
The next step should be
A) CT scan of chest, abdomen and pelvis
B) Observation
C) Fine needle aspiration of the cervical nodes
D) Excisional biopsy of a cervical node
Her pathology returns diffuse large cell lymphoma.
After discussion of her diagnosis with her, the next
most appropriate step in her management would be:
A) Referral to general surgery for debulking of all
disease
B) Check a GHS and begin chemotherapy with ABVD
C) Check a b2MG, LDH, and ESR
D) CT scan of chest, abdomen, and pelvis
Her CT scan returns with a mediastinal mass that
measures 12 cm as well as many nodes in her abdomen,
the largest being 3 cms.
She has a bone marrow that is negative for disease.
What is the stage of her disease?
A) IIB
IIIBE
C) IIBX
D) IIIAX
E) IV
B)
Staging system
Ann Arbor
Stage I
1 node or group
Stage II
2 or more lymph node groups, same
side of the diaphragm
Stage III
Spans the diaphragm
Stage IV
Disseminated disease
Subscripts with the staging system include
A --B symptoms absent
B --B symptoms present
X --Bulky disease --defined as any mass >10
cms or a mass > 1/3 the diameter of the chest
E –Extranodal disease
You have now determined that your patient has stage
IIIAX disease. She asks your advice concerning
treatment options. You should tell her:
A) She does not yet need treatment
She should not agree to treatment as there is none
with proven efficacy
C) She should receive radiation therapy to her
mediastinal mass followed by rituxan
D) Multiagent chemotherapy will offer her a chance for
cure
B)
Bimodal age distribution
Often see the “B” symptoms
Fever
Night sweats
Weight loss
Pruritus is common
Unusual complaint of pain with alcohol ingestion
Classification includes
Lymphocyte Predominant
Mixed Cellularity
Nodular Sclerosing
Lymphocyte Depleted
Prognosis is most closely linked to stage of disease
Stage IA with survival rate of >90%
Stage IV with survival rate of >60%
Long term complications after treatment for Hodgkin
Disease are common and include
Hypothyroidism
Infertility
Secondary malignancy including
MDS/AML
Solid tumors such as Breast and Lung
Most are B cell in origin
Incidence is increasing in Western countries
Many associated with immunodeficiency states
Burkitt’s lymphoma==L3
Endemic
Epidemic
African variety
US
Jaw mass
Abdominal mass
EBV +++
EBV +/-
Lymphoblastic lymphoma ==ALL
Typically young adults and children
Frequently a mediastinal mass at presentation
Often Stage IV at presentation
CNS involvement is common
H PYLORI ASSOCIATED
MALT
EBV ASSOCIATED
POST TRANSPLANT NHL
HTLV-1 ASSOCIATED
ATLL
A 72 year old man is seen for routine check up. He has
no complaints and his physical exam is benign.
Screening lab is as follows:
Hgb 12.0
Tprot 10
HCT 37
Alb 2.0
WBC 3300
AST 67
Plts 460,000
ALT 80
Work up should include which of the following?
A) Liver biopsy
B) Bone marrow aspirate and biopsy
C) SPEP/UPEP
D) Beta-2-Microglobulin
Clues include
A low anion gap
Rouleaux on peripheral
smear
An elevated globulin
fraction (TP-Alb)
95% will have an abnormal protein on SPEP or UPEP
The M spike is most commonly IgG followed by IgA,
light chain disease,and IgD
<5% will be non-secretory and have no evidence of
protein secretion
MGUS
MM
<10% PLASMA
>30% PLASMA
CELLS
< 3 GRAMS
PROTEIN
NO LYTIC
LESIONS
CELLS
>3.5 GRAMS
PROTEIN
+/- LYTIC
LESIONS
Affects about 5% of patients over 70
About 25% will progress to MM over about 10 years
No treatment required
Follow lab studies every 6 months
MULTIPLE MYELOMA
Treat for progressive disease
BMT accepted treatment for MM
Solitary plasmacytoma becomes MM in most patients
over time
Increased IgM levels
More common in older men
Presentation is usually with
Lymphadenopathy/organomegaly
Purpura
Neuropathy
Hyperviscosity syndrome
Cells best described as “plasmacytoid lymphocytes”
Pluripotent cells found in the bone marrow
Rare (less than 1 in 100,000 cells)
No identifiable morphological characteristics
CD 34 + (stem cell antigen)
Can be induced to circulate
in the peripheral blood
Need 2.0–5.0 x 106 CD 34 + cells/kg
of recipient body weight
Cell sources:
HPSCT
BONE MARROW
PBSC
Types of transplants:
HPSCT
AUTOLOGOUS
ALLOGENEIC
Use patient’s own cells
Has less acute mortality
Higher relapse rate
Some accepted indications for autologous
transplant include:
Lymphoma including NHL and HD
Leukemia including AML and ALL in CR
Multiple Myeloma
Breast cancer is controversial
Testicular cancer for
relapsed disease
Related donor or unrelated donor(NMDP)
Has a higher acute mortality rate
Less relapse risk
Some accepted indications
for allogeneic transplant
Chronic leukemia including CML and CLL
Relapsed acute leukemia including
AML and ALL
Myelodysplasia
Multiple myeloma (VIC)
GVHD—a unique toxicity to allogeneic
transplant—higher risk with unrelated donor
source; may be fatal; acute looks like fever, skin
rash, GI track involvement; chronic looks like
scleroderma
GV“T”—a benefit of GVHD is graft vs. tumor
effect, which may decrease relapse rate—
mediated by T lymphocytes